Med Phys Alumni Series: How do polymyxin antibiotics kill bacteria?

Join us for a fascinating lunchtime seminar led by MEng Biomedical Engineering alumna Carolina Borrelli, who explores the molecular mystery behind polymyxin antibiotics, vital last-resort treatments in the fight against antimicrobial resistance.

Based on her recent findings, published in Nature Microbiology.

This event is hybrid. If you would like to register to attend online, please click here >>>

How do polymyxin antibiotics kill bacteria?

Antimicrobial resistance poses a major global health risk. Infections that were once simple to cure can become life-threatening as bacteria develop resistance to previously effective drugs. This challenge impacts not only common illnesses but also critical medical procedures such as surgeries and cancer therapies.

Rising resistance rates have forced reliance on older antibiotics, such as polymyxins, as last-resort treatments despite their limited effectiveness. Discovered over 80 years ago, polymyxins are used to treat infections caused by Gram-negative bacteria such as Escherichia coli. These kinds of bacteria possess an outer membrane that helps block many antibiotics from entering the cell. While polymyxins are known to attack this protective layer, the precise way in which they disrupt it and successfully kill the bacteria remains unclear. 

By employing a mix of biochemical and biophysical methods, including Atomic Force Microscopy, we investigated how polymyxin B (PmB) acts at the molecular level in dormant and active bacteria. We demonstrate that metabolic activity is essential for the lethality of clinically relevant doses of PmB and leverage this insight to determine its mode of action. PmB killed exponential-phase E. coli but did not eliminate stationary-phase cells unless a carbon source was available.